..In conclusion, studies of the regulation of A beta production and aggregation in cell culture can provide information under physiological conditions that can complement analyses of these processes in vivo...

Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma

..Abeta distribution in plasma was not significantly influenced by apolipoprotein E genotype. We conclude that Abeta is normally bound to and transported by albumin and specific lipoproteins in human plasma under physiological conditions...

Notch and presenilins in vertebrates and invertebrates: implications for neuronal development and degeneration

..This previously neglected topic has begun receiving serious attention. Understanding how proteolysis regulates Abeta levels in the cerebral cortex has implications for both the pathogenesis and the treatment of this protean disorder...

Introducing transglutaminase into the study of Alzheimer's disease. A personal look back

..Thus, PSs are complexed with the gamma-secretase substrates C83 and C99 in the subcellular locations where Abeta is generated, indicating that PSs are directly involved in the pathogenically critical intramembranous proteolysis of APP...

Presenilin 1 regulates the processing of beta-amyloid precursor protein C-terminal fragments and the generation of amyloid beta-protein in endoplasmic reticulum and Golgi

..Our results indicate PS1 and APP can interact in the ER and Golgi, where PS1 is required for proper gamma-secretase processing of APP CTFs, and that PS1 mutations augment Abeta42 levels principally in Golgi-like vesicles...

Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity

..Our results indicate that presenilins are rapidly processed to N- and C-terminal fragments in both neural and nonneural cells and that interference with this processing is not an obligatory feature of FAD-causing mutations...

Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signaling

..We conclude that AMY IR represents an amyloid-associated antigen that co-deposits in most but not all Abeta plaques in AD and DS and that accumulation of the AMY antigen follows Abeta deposition in plaques...

..Together with our earlier observations, these results suggest that alphaS-PUFA interactions help regulate neuronal PUFA levels as well as the oligomerization state of alphaS, both normally and in human synucleinopathies...

A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference

..These results suggest that the potential to form fibrils under physiologic conditions is not limited to those proteins associated with amyloidoses and that fibril formation alone is not predictive of cytotoxic activity...

The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease

..An interaction model involving both domains and looping of interjacent DNA is proposed. We conclude that this newly described binding protein-enhancer complex is required for full betaAPP promoter activation...

Nasal vaccination with beta-amyloid peptide for the treatment of Alzheimer's disease

..These results provide evidence for the role(s) of naturally occurring free D-Asp in mammalian physiology. The findings argue against the conventional concept that only L-stereoisomers of amino acids are functional in higher species...

..The progress reviewed here, coupled with better ability to diagnose the disease early, bode well for the successful development of therapeutic and preventative drugs for this major public health problem...

..Taken together, our results demonstrate that Pen-2 interacts with PS-NTF within active gamma-secretase and offer a model for how the components of active gamma-secretase interact physically with each other...

..Furthermore, we find no change in plaque deposition or in peripheral Abeta levels. Data from these Alzheimer models suggest that captopril and similar ACE inhibitors do not cause Abeta accumulation in vivo...

Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1

..Finally, we find that Miro and Milton expression suppresses altered mitochondrial morphology induced by loss of Pink1 function in cell culture. Our findings suggest that Pink1 functions in the trafficking of mitochondria in cells...

..These results are consistent with the putative role of beta PP in cell adhesion and suggests that beta PP either interacts with selected integrins or shares similar cellular machinery to promote cell adhesion...

..These results indicate that specific inhibition of this A beta-generating protease is possible in living human neural cells and provide information about the characteristics of this as yet unidentified enzyme...

Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein

..We conclude that gamma-secretase can cleave near the middle of the Notch TMD, that Abeta-like peptides may arise during Notch processing, and that the pre-TMD sequence of the substrate influences recognition or binding by the enzyme...

..This understanding of the genotype-to-phenotype conversions of familial AD has led to the development of pharmacological strategies to lower amyloid beta-protein levels as a way of treating or preventing all forms of the disease...

..Most of the Abeta in the serum of the immunized mice was bound to antibodies. We conclude that following active immunization, anti-Abeta antibodies sequester serum Abeta and may increase central nervous system to serum Abeta clearance...

Aging, amyloid, and Alzheimer's disease: a perspective in honor of Carl Cotman

..A common theme has arisen in this field: normally-soluble proteins accumulate, misfold and oligomerize, inducing cytotoxic effects that are particularly devastating in the post-mitotic milieu of the neuron...

..Our results identify a novel, catalytically inefficient form of IDE expressed in brain and non-neural tissues and recommend novel regions of the IDE gene in which to search for mutations predisposing patients to AD and DM2...

..While hard work lies ahead, the movement from basic research to the clinic in AD represents a triumph of reductionist biology applied to the most complex of all biological systems, the human cerebral cortex...

..Research is ongoing to determine if these early network alterations will serve as sensitive predictors of clinical decline, and eventually, as markers of pharmacological response to potential disease-modifying treatments for AD...